Review of Post Authorization Safety Data for Janssen

COVID-19 Vaccine

Narayan Nair, MDDivision Director– Division of Epidemiology,

Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, FDA

October 25, 2021

My comments are an informal communication and represent my own best

judgment. These comments do not bind or obligate FDA.

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Overview

• Passive Surveillance Safety Data from Vaccine Adverse

Event Reporting System (VAERS)

– Existing Safety Concerns

– Potential Emerging Safety Concerns

• Summary of FDA Active Surveillance

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Janssen COVID-19 Vaccine

• February 27, 2021, the US Food and Drug Administration (FDA)

issued an Emergency Use Authorization (EUA) for

Janssen/Johnson & Johnson COVID-19 vaccine,

• The Janssen COVID-19 Vaccine uses a replication-incompetent

human adenoviral type 26 vector platform (Ad26.COV2.S)

• 14,688,615 doses of vaccine administered in U.S.

(as of October 7, 2021)

Vaccine RecipientsVaccination Providers

Vaccine EUA Sponsor

Mandatory Reporting• Vaccination administration errors

(providers only)• Serious adverse events (SAEs)• Multisystem Inflammatory

Syndrome • Cases of COVID-19 that result in

hospitalization or death

• Screening of all incoming SAEs• Literature review• Data Mining• Potential safety signals will be

further evaluated

• Review of all Adverse Events of Special Interest (AESI)

• Data Abstraction

Voluntary Reporting• Spontaneous reports • Solicited reports from

v-safe program

Coordination Data Sharing

Adverse Event Reporting under EUA

Monthly Periodic Safety Reports

• Analysis of aggregate AE data

• Newly identified safety concerns

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Strengths

– Rapidly detects potential safety problems

– Potential detection of rare adverse events

– Open-ended for hypothesis generation

– Geographic diversity

– Capability to monitor production lots

Limitations

– Missing and/or inaccurate data

– Reported diagnoses are not verified

– Under-reporting

– Reporting bias (stimulated reporting)

– Absence of unvaccinated control group

– Inability to assess causation

– Not likely to detect long latency events

Vaccine Adverse Event Reporting System

• Passive surveillance of vaccines• Nation’s early warning system for vaccine safety• VAERS accepts all reports regardless of the plausibility of the vaccine

causing the event or the clinical seriousness of the event

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Summary of Existing Safety Concerns -

Thrombosis with Thrombocytopenia Syndrome

• Post authorization surveillance in VAERS identified reports of cerebral venous sinus thrombosis (CVST) and thrombosis with thrombocytopenia syndrome (TTS) after Janssen COVID-19 Vaccine*

• On 4/13/21, use of the vaccine in the US was paused because of concerns about a potential association with the vaccine.

• On 4/23/21, the Fact Sheets were updated to include a Warning about TTS and the pause was lifted

• As of 10/5/21, 47 cases of TTS have been confirmed after Janssen COVID-19 Vaccine

• Evaluation of this safety issue is ongoing

*See I, Su JR, Lale A, Woo EJ, Guh AY, Shimabukuro TT, Streiff MB, Rao AK, Wheeler AP, Beavers SF, Durbin AP. US case reports of cerebral

venous sinus thrombosis with thrombocytopenia after Ad26. COV2. S vaccination, March 2 to April 21, 2021. JAMA. 2021 Apr 30

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Summary of Existing Safety Concerns

- Guillain-Barré Syndrome (GBS)

• Post-authorization surveillance in VAERS identified 130 reports of GBS after Janssen vaccine as of 7/24/2021

– Observed reports > expected across multiple age groups, without respect to Brighton Collaboration criteria

– Reporting rate for GBS is higher for Janssen than for mRNA vaccines

• Estimated observed-to-expected rate ratio was 4.18*

• On 7/12/21, EUA Fact Sheets were updated to include new information about GBS

* Woo EJ, Mba-Jonas A, Dimova RB, Alimchandani M, Zinderman CE, Nair N. Association of Receipt of the

Ad26.COV2.S COVID-19 Vaccine With Presumptive Guillain-Barré Syndrome, February-July 2021. JAMA.

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Summary of Potential Emerging Safety

Concerns – Myocarditis and Pericarditis

• Post authorization surveillance of VAERS has identified a potential emerging safety concern regarding myocarditis and pericarditis

• As of 8/27/21, 93 reports of myocarditis/pericarditis in VAERS following the Janssen COVID-19 Vaccine (non-adjudicated)

• Based on preliminary review, the estimated observed-to-expected values were elevated for all adults 18 and older, with significant elevations in both sexes, various age strata, different risk windows, and different background rates with reporting rate ratio of 4.14 (3.20, 5.27)

• There were five death reports, all in people 30 or older and three in women

• Evaluation of myocarditis and pericarditis is ongoing

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Summary of Potential Emerging Safety

Concerns – Thromboembolic Events (TEE)

• Post authorization surveillance of VAERS has identified a potential emerging safety

concern regarding TEE

• As described in the Fact Sheets, section 6.1 Clinical Trials Experience, numerical

imbalances, with more events in vaccine than placebo recipients, were observed for TEE

(deep vein thrombosis; pulmonary embolism; transverse sinus thrombosis with

thrombocytopenia).

• As of 10/4/2021, 2,792 reports of TEE in VAERS following the Janssen COVID-19

Vaccine (non-adjudicated)

• Evaluation of TEE is ongoing

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Summary of Potential Emerging Safety

Concerns – Immune Thrombocytopenia

(ITP)

• Post authorization surveillance of VAERS has identified a potential emerging safety concern regarding ITP

• As of 10/4/2021, 185 reports of ITP in VAERS following the Janssen COVID-19 Vaccine (non-adjudicated)

• FDA preliminary analysis found the number observed exceeded the number expected with reporting rate ratio of 1.37 (1.18, 1.58)

• Evaluation of ITP reports is ongoing

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Active Surveillance in FDA BEST System:

Near Real-Time Surveillance of Janssen COVID-19 Vaccine

Data cutoff: Optum: 9/18; Health Core (HCI) :7/10, Medicare FFS (CMS): 9/11 Risk Window: An interval during which occurrence of the AESI will be included in the analyses*CMS – 65 years and older **cerebral and abdominal

***acute myocardial infraction, deep vein thrombosis, pulmonary embolism, hemorrhagic stroke, non-hemorrhagic stroke

Adverse Event of Special

Interest (AESI)

Risk

Window

Number of AESI post-vaccination

(Number of Janssen Vaccine Doses) Signal in Testing

CMS*

(406,451)

Optum

(197,553)

HCI

(224,609)

CMS* Optum HCI

Guillan-Barre Syndrome 1-42 N<11 N<11 N<11 No No No

Unusual site thromboses**with thrombocytopenia

1-28 N<11 N<11 N<11 No No No

Common site thromboses*** with thrombocytopenia

1-28 139 N<11 N<11 No No No

Deep vein thrombosis 1-28 397 39 31 No No No

Pulmonary embolism 1-28 296 32 28 No No No

Myocarditis/Pericarditis 1-42 39 N<11 11 No No No

Immune thrombocytopenia 1-42 57 11 N<11 No No No

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Summary of Post-authorization Safety Data following the Janssen

Vaccine

• FDA and CDC continue to follow cases of GBS, and TTS reported to VAERS following Janssen COVID-19 vaccination – Information regarding these adverse events are currently communicated

in EUA Fact Sheets

• FDA and CDC continue to assess cases of myocarditis, pericarditis, ITP, TEE reported to VAERS following Janssen COVID-19 vaccination – Preliminary analysis of unadjudicated cases in VAERS reveal an increased

observed to expected ratio of myocarditis/pericarditis, and ITP

• FDA Near Real-Time Surveillance of 16 potential outcomes does not reveal safety signals for these adverse events at this time

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Acknowledgments

CBER

• Jane Woo

• Adamma Mba-Jonas

• Meghna Alimchandani

• Steve Anderson

• Rich Forshee

• Rositsa Dimova

• Hui Lee Wong

• David Menschik

• Craig Zinderman

• CBER Surveillance Team

Partners

• Acumen

• Optum

• Healthcore

• Centers for Disease Control and Prevention

Backup Slides

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Optum HealthCore (HCI)

Overall description

Health insurance enrollment, demographic, and

longitudinal health information for commercially

insured and Medicare Advantage enrollees

Health insurance enrollment, demographic, medical claims, pharmacy claims and laboratory results

from the HealthCore Integrated Research Environment (HIRE), which contains longitudinal

health information for Anthem insured and Medicare Advantage enrolled individuals

Health plans Optum affiliated health plans Anthem

Time period December 2017-Present 2010-Present

Average Number of

Annual Enrollees~14.5 million 20-25 million

Data lag ~ 2 months for IP at 90% completenessThe data lag is 3 months for complete data and is 1-3 months for pharmacy dispensings and early settled

outpatient claims

Limitations

Claims data was sourced before the adjudication

process (which allowed for data to be analyzed

more quickly – data is available for claims with

dates of service through 9/18)

Data is currently only available for claims with dates

of service through 7/10 for the RCA and through

8/5 for the descriptive analysis of booster

vaccinations

Description of Commercial Claims Data Sources in BEST Initiative

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FDA BEST Initiative: Booster VaccinationsBrand and Dose CMS (Data through 9/4) Optum (Data through 9/18) HCI (Data through 8/5)

Number of Vaccinations

Percentage of Total Booster Vaccinations*

Number of Vaccinations

Percentage of Total Booster Vaccinations*

Number of Vaccinations

Percentage of Number of

Vaccinations*

Total Booster Vaccinations 82,129 100 67,698 100 6,603 100

Dose 2 following Janssen 2,242 2.6 5,163 7.6 963 14.6

Janssen 1,051 1.2 1,275 1.9 179 2.7

Moderna 603 0.7 1,546 2.3 409 6.2

Pfizer 588 0.7 2,342 3.5 375 5.7

Dose 3 following Moderna Dose 2 44,014 51.7 28,514 42.1 3,255 49.3

Janssen 274 0.3 115 0.2 37 0.6

Moderna 42,085 49.4 27,130 40.1 2,876 43.6

Pfizer 1,655 1.9 1,269 1.9 342 5.2

Dose 3 following Pfizer Dose 2 38,873 45.7 34,021 50.3 2,385 36.1

Janssen 330 0.4 138 0.2 37 0.6

Moderna 1,619 1.9 1,435 2.1 769 11.6

Pfizer 36,924 43.4 32,448 47.9 1,579 23.9

*Strata percentages may not sum to 100% due to

rounding